The goal of the proposed study is to design, fabricate and test an optimal thrombectomy catheter for treatment of ischemic stroke. The size/extent of ischemic damage following a stroke may be dramatically reduced (and the time window for IV-tPA extended) by mechanically removing the thrombus and providing local treatment. Currently, no such treatments are available/approved by the FDA for clinical use. Our novel catheter-based, approach exploits the phenomenon of fluidic streaming, actuated via a simple and inexpensive system, to fragment the clot. The high shear and low pressure generated as a result of the induced fluid motion will embolize the clot, with minimal associated blood vessel damage or hemolysis. Since no anti-thrombotic agents are needed, hemorrhagic side effects are minimized. The catheter will be fully compatible with current interventional neuro-radiological procedures and accessorial equipment. The proposed concept will also provide the flexibility to deliver anti-thrombotic/preventive treatments locally. Optimal design will be arrived at using a combination of computational and experimental investigations. Design alternatives will be evaluated using CFDRC-developed state-of-the-art multiphysics simulations, and the most promising design will be chosen for prototype manufacturing. Thrombolytic performance will be established through in-vitro experimental flow studies. Phase II will involve further computational design optimization and fabrication followed by in vitro experiments and animal model testing of clinical grade catheters. Extensive consultation will be provided by a multi-disciplinary team of clinical users (Vascular and Neuro Surgery Departments, University of Chicago), clinical researchers (Biomedical Eng., liT Chicago) and a commercial manufacturer of catheters (Spire Biomedical, MA). The optimal thrombectomy catheter developed in this study will immediately benefit the approximately 1 million U.S (10 million worldwide) patients that suffer ischemic stroke. The $260 million interventional neuro device markets is growing 20-25% annually and should continue to do so for the foreseeable future. The device will be marketed and/or licensed to present catheter manufacturers such as Spire Biomedical, Guidant, Boston-Scientific, J&J, etc, who in turn will offer the device to healthcare professionals. This approach can also be readily extended to other thrombectomy applications such as in cardiac circulation, peripheral vasculature etc.